The 22 amino acid peptide, motilin, was isolated from porcine gut in 1971, and the amino acid sequence was determined. Analogous proteins having a high degree of homology have been isolated from the- gut of other species, including canine and rabbit. Present evidence indicates that motilin acts on the cholinergic neurons of the enteric plexis, and is associated with cyclic motor activity of the intestine.
Other tissues besides the gut have been assayed for the presence of motilin by immunoreaction using antisera prepared using immunization against natural porcine motilin, portions of the amino terminal and carboxy terminal portions of motilin, and a synthetic (14-Met) motilin. These assays gave conflicting results depending on the antisera chosen. One or another of these antisera reacts with a protein found in stomach, gall bladder, adrenals, salivary glands, cerebrospinal fluid, cerebral cortex, brain stem, hypothalamus, medulla, pituitary, pineal glands, and fibers of various sympathetic nerves. The inconsistent results obtained using various antisera has been considered by some to be evidence that motilin exists in different molecular weight forms (Pearse, A.G.E , et al, Virchows Archive Cell Pathol (1974) 16:111-120; Polak, J. M., et al, Gut (1975) 16:225-229; Polak, J. M., et al, Scand J Gastroent (1976) 11 (Suppl 39):39-42).
While it has been established that motilin plays an important role in the nutrition of vertebrates, its tissue of origin and control of its production have not been established. Accordingly, coordination of motilin levels in appropriate tissues with desired responses has not been possible. It has now been shown, using recombinant technology, that this peptide originates in the intestine. More important, it has now been shown that an unpredicted additional peptide, motilin-associated peptide (MAP), is encoded contiguous with the codons for motilin. MAP thus provides an additional tool for manipulation of the psychology and physiology of alimentation.